Synthesis cases
Five integrated cases that pull threads from across the curriculum. Each one is best worked in writing — identify the cellular processes, the evidence grade behind your reasoning, and the ambiguity that remains.
Case 1 — A 9-month-old with hypotonia and rising lactate
Integrate mitochondrial bioenergetics (Module 7), proteostasis (Module 3), and signal transduction (Module 8) to build a differential. Which assays distinguish a respiratory-chain disorder from a fatty-acid oxidation defect? What does heteroplasmy predict about tissue presentation?
Case 2 — Newly diagnosed BRCA1-mutated triple-negative breast cancer
Argue, from DNA damage repair (Module 13), cell cycle (Module 11), and cancer cell biology (Module 14), why olaparib + platinum is rational. Predict the principal resistance mechanisms and how a checkpoint-blockade combination might mitigate them.
Case 3 — Refractory CLL going on venetoclax + obinutuzumab
Explain the BCL-2 dependency (Module 12), the antibody-mediated cytotoxicity (Module 16), the tumour-lysis risk in cell-cycle terms (Module 11), and one mechanism by which the tumour will eventually escape.
Case 4 — A young adult with sickle cell disease considering Casgevy
Walk through gene-expression rewiring of BCL11A (Module 9), chromatin context (Module 9), HSC biology (Module 15), the manufacturing chain, conditioning toxicity, and the evidence base (Module 18). What would you tell the patient about durability and risk?
Case 5 — A 'longevity clinic' offering NAD precursors and senolytics
Using bioenergetics (Module 7), cell death (Module 12), and the translational frontier (Module 18) — and the Evidence Grader page — write the counselling note you would give a patient.
For each case, write out: (1) which cells and compartments are central; (2) which molecular machinery is implicated; (3) what evidence grade supports your reasoning; (4) what would falsify it.